Researcher: Başpınar, Alper
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Başpınar, Alper
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Publication Open Access PRISM: a web server and repository for prediction of protein-protein interactions and modeling their 3D complexes(Oxford University Press (OUP), 2014) Nussinov, Ruth; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Başpınar, Alper; Çukuroğlu, Engin; Keskin, Özlem; Gürsoy, Attila; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 26605; 8745The PRISM web server enables fast and accurate prediction of protein-protein interactions (PPIs). The prediction algorithm is knowledge-based. It combines structural similarity and accounts for evolutionary conservation in the template interfaces. The predicted models are stored in its repository. Given two protein structures, PRISM will provide a structural model of their complex if a matching template interface is available. Users can download the complex structure, retrieve the interface residues and visualize the complex model.Publication Open Access The structural network of Interleukin-10 and its implications in inflammation and cancer(BioMed Central, 2014) Chen, Zhong; Van Waes, Carter; Nussinov, Ruth; Department of Computer Engineering; Özbabacan, Saliha Ece Acuner; Engin, Hatice Billur; Maiorov, Emine Güven; Kuzu, Güray; Muratçıoğlu, Serena; Başpınar, Alper; Gürsoy, Attila; PhD Student; Faculty Member; Department of Computer Engineering; The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; N/A; N/A; N/A; N/A; N/A; N/A; 8745Background: Inflammation has significant roles in all phases of tumor development, including initiation, progression and metastasis. Interleukin-10 (IL-10) is a well-known immuno-modulatory cytokine with an anti-inflammatory activity. Lack of IL-10 allows induction of pro-inflammatory cytokines and hinders anti-tumor immunity, thereby favoring tumor growth. The IL-10 network is among the most important paths linking cancer and inflammation. The simple node-and-edge network representation is useful, but limited, hampering the understanding of the mechanistic details of signaling pathways. Structural networks complete the missing parts, and provide details. The IL-10 structural network may shed light on the mechanisms through which disease-related mutations work and the pathogenesis of malignancies. Results: Using PRISM (a PRotein Interactions by Structural Matching tool), we constructed the structural network of IL-10, which includes its first and second degree protein neighbor interactions. We predicted the structures of complexes involved in these interactions, thereby enriching the available structural data. In order to reveal the significance of the interactions, we exploited mutations identified in cancer patients, mapping them onto key proteins of this network. We analyzed the effect of these mutations on the interactions, and demonstrated a relation between these and inflammation and cancer. Our results suggest that mutations that disrupt the interactions of IL-10 with its receptors (IL-10RA and IL-10RB) and alpha 2-macroglobulin (A2M) may enhance inflammation and modulate anti-tumor immunity. Likewise, mutations that weaken the A2M-APP (amyloid precursor protein) association may increase the proliferative effect of APP through preventing beta-amyloid degradation by the A2M receptor, and mutations that abolish the A2M-Kallikrein-13 (KLK13) interaction may lead to cell proliferation and metastasis through the destructive effect of KLK13 on the extracellular matrix. Conclusions: Prediction of protein-protein interactions through structural matching can enrich the available cellular pathways. In addition, the structural data of protein complexes suggest how oncogenic mutations influence the interactions and explain their potential impact on IL-10 signaling in cancer and inflammation.